Insulin and IGFs in renal cancer risk and progression

Endocr Relat Cancer. 2015 Oct;22(5):R253-64. doi: 10.1530/ERC-15-0135.

Abstract

Insulin and IGFs play a significant role in cancer development and progression, including renal cell carcinoma (RCC). RCC is the most frequent type of kidney cancer in adults and the tenth most common malignancy worldwide. Insulin is normally associated with metabolism control, whereas IGFs are defined as proliferation regulators. Today, there is convincing evidence of an association between obesity and the risk of RCC. Indicated risk factors together with type 2 diabetes are irreversibly connected with circulating insulin and IGF levels. The interplay between these molecules, their receptors, and IGF-binding proteins might be crucial for RCC cell biology and RCC progression. Given the potent activity IGF/IGF receptor 1 (IGF1R) inhibitors demonstrate against RCC in basic research, some type of combination therapy may prove to be beneficial clinically in the management of RCC. This review addresses not only molecular but also clinical associations between insulin and IGF1 signaling pathways and both RCC biology and clinical course. Revealing these interactions may improve our understanding of basic molecular oncology processes in RCC and improve treatment strategies.

Keywords: diabetes mellitus; insulin; insulin receptor; insulin-like growth factor; insulin-like growth factor receptor; obesity; renal cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Disease Progression
  • Humans
  • Insulin / metabolism*
  • Insulin-Like Growth Factor Binding Proteins / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Kidney Neoplasms / etiology*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Risk Factors

Substances

  • Insulin
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I